Acceleration of ageing via disturbing mTOR-regulated proteostasis by a new ageing-associated gene PC4.
PC4
ageing
mTOR
protein synthesis
proteostasis
Journal
Aging cell
ISSN: 1474-9726
Titre abrégé: Aging Cell
Pays: England
ID NLM: 101130839
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
revised:
21
02
2021
received:
27
11
2020
accepted:
31
03
2021
pubmed:
7
5
2021
medline:
29
12
2021
entrez:
6
5
2021
Statut:
ppublish
Résumé
Research on ageing-associated genes is important for investigating ageing and anti-ageing strategies. Here, we firstly reported that the human positive cofactor 4 (PC4), a multifunctional and highly conserved nucleoprotein, is accumulated and activated during ageing and causes global accelerated ageing process by disrupting proteostasis. Mechanistically, PC4 interacts with Sin3-HDAC complex and inhibits its deacetylated activity, leads to hyper-acetylation of the histones at the promoters of mTOR-related genes and causes mTOR signalling activation. Accordingly, mTOR activation causes excessive protein synthesis, resulting in impaired proteostasis and accelerated senescence. These results reveal a new biological function of PC4 in vivo, recognizes PC4 as a new ageing-associated gene and provides a genetically engineered mouse model to simulate natural ageing. More importantly, our findings also indicate that PC4 is involved in histone acetylation and serves as a potential target to improve proteostasis and delay ageing.
Identifiants
pubmed: 33957702
doi: 10.1111/acel.13370
pmc: PMC8208792
doi:
Substances chimiques
DNA-Binding Proteins
0
SUB1 protein, human
0
Transcription Factors
0
MTOR protein, human
EC 2.7.1.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13370Informations de copyright
© 2021 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
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